title: Targeting the BMK1 MAP kinase pathway in cancer therapy.
abstract: The big mitogen activated protein kinase 1 (BMK1) pathway is the most recently discovered and least-studied mammalian mitogen-activated protein (MAP) kinase cascade, ubiquitously expressed in all types of cancer cells tested so far. Mitogens and oncogenic signals strongly activate this cellular MAP kinase pathway, thereby passing down proliferative, survival, chemoresistance, invasive, and angiogenic signals in tumor cells. Recently, several pharmacologic small molecule inhibitors of this pathway have been developed. Among them, the BMK1 inhibitor XMD8-92 blocks cellular BMK1 activation and significantly suppresses tumor growth in lung and cervical tumor models and is well tolerated in animals. On the other hand, MEK5 inhibitors, BIX02188, BIX02189, and compound 6, suppress cellular MEK5 activity, but no data exist to date on their effectiveness in animals.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Qingkai
authors.initials: Q
authors.lastname: Yang
authors.forename: Jiing-Dwan
authors.initials: JD
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D006801:Humans; D048671:MAP Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic
chemical_list: D000970:Antineoplastic Agents; D001570:Benzodiazepinones; C568790:XMD 8-92; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human